Proteomic Screening of Human Targets of Viral microRNAs Reveals Functions Associated with Immune Evasion and Angiogenesis

PLoS Pathogens

Christine Happel¹  Amelia M. Gallaher¹  Philippe Kieffer-Kwon¹  Joseph Ziegelbauer¹  Zhen Xiao²  Thorkell Andresson²  Sudipto Das² 

[1] HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America;Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, Maryland, United States of America

关键词: MicroRNAs;    Protein expression;    Gene expression;    Microarrays;    Stable isotope labeling by amino acids in cell culture;    Kaposi's sarcoma-associated herpesvirus;    Endothelial cells;    Messenger RNA;   

DOI  :  10.1371/journal.ppat.1003584

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Kaposi's sarcoma (KS) is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV). The virus expresses unique microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC) in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1) following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1α), and up-regulation of a protein involved in stimulating angiogenesis (HMOX1). This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis.

【 授权许可】

CC BY